Year: 2011
Type: article
Abstract: Notch receptors and their ligands have crucial roles in development and tumorigenesis. We present evidence demonstrating the existence of an antagonistic relationship between Notch 4 and Trp53, which is controlled by the Mdm2-dependent ubiquitylation and degradation of the Notch receptor. We show that this signal-controlling mechanism is mediated by physical interactions between Mdm2 and Notch 4 and suggest the existence of a trimeric complex between Trp53, Notch 4 and Mdm2, which ultimately regulates Notch activity. Functional studies indicate that Trp53 can suppress NICD4-induced anchorage-independent growth in mammary epithelial cells and present evidence showing that Trp53 has a pivotal role in the suppression of Notch-associated tumorigenesis in the mammary gland.
Source: Journal of Cell Science
DOI: 10.1242/jcs.068965
Authors: Youping Sun, Malgorzata Klauzinska, Robert J. Lake, Joseph M. Lee, Stefania Santopietro, Ahmed Raafat, David Salomon, Robert Callahan, Spyros Artavanis-Tsakonas
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2031350022